BACKGROUND: At ASCO 2001, we introduced the Cervical Acid Phosphatase – Papanicolaou
(CAP-PAP) test as a new, biomarker-driven technology for detection
of abnormal cervical cells on Pap smears. Since this report, we conducted
two clinical trials to assess the value of this test for cervical cancer
screening in general (N=1,500) and a high-risk population (N=500).
This technology is commercially available as the MarkPap™ Research
Kit (BioSciCon, Inc., Rockville, MD, USA). METHODS: Multicenter, random
assignment, assessors blinded, split sample, concurrent control 3-group
(test and two controls [Pap smears and ThinPrep thin layers] clinical
trial was conducted on 1,500 specimens obtained from eligible subjects
coming for regular Pap test. Specimens collected in PreservCyt® and
transferred onto microscopic slides using the ThinPrep Processor 2000
were split in two samples before processing. Specimens obtained with
cervical epithelium abrading devices, were split by the physician in
two samples (smears). Primary efficacy endpoints were the portion of
detected abnormal samples and the portion of false negative readings.
Accuracy was measured against a cytology standard (association or adjudication).
RESULTS:

Comparison between test and control groups

Subgroup A:
MPT vs. ThP

Subgroup B:
MPT vs. Pap smears

Evaluation

MPT vs. ThP

MPT vs. Pap

Number of samples

348

1,039

25%

75%

Association

0.86 [Y+, or Y-]

0.83 [Y+, or Y-]

Consensus standard

Discrepancy

0.14 [N+-, or N-+]

0.17 [N+-, or N-+]

Adjudicated standard

Abnormal samples

0.097

0.103

0.157

0.049

[Pe -Ps] ≤ δ*

Pe ≤ Ps+δ

False negatives

-

-

0.04

0.09

-

Pe < Ps - δ

Sensitivity

0.45

0.60

0.837

0.513

[Pe-Ps] ≤ δ

Pe > Ps+δ

Specificity

0.95

0.98

0.948

0.995

[Pe-Ps] ≤ δ

[Pe-Ps] ≤ δ

CONCLUSION: This data suggests that the new technology is more sensitive
(with equivalent specificity) than either conventional Pap smear or ThinPrep
Pap test. However, when specimens were collected in PreservCyt®,
due to alcohol inhibition of the enzyme, this sensitivity was reduced.
This work was supported in part by NCI, NIH, via SBIR Phase-1 and Phase-2
grants: 1 R43CA086767-01, and 2-R44CA086767-02.